Studies on the mechanism of inhibition of red cell sickling by glyceraldehyde will be continued. We have identified the three major sites of Schiff-base formation of glyceraldehyde with hemoglobin S as Val-l (beta), Lys-82 (beta), and Lys-16 (alpha). We will determine which of these sites is responsible for the antisickling effects of glyceraldehyde by studies of hybrids that contain only one of the above sites as a Schiff base with the aldehyde. These hybrids will be prepared in a manner analogous to that used for the preparation of the carbamylated hybrids of hemoglobin S. The studies on the sites of binding of small inorganic anions to hemoglobin will be continued in collaboration with Dr. J.O. Alben of Ohio State University. Finally, we will analyze samples for the group at the University of Washington in Seattle where an apparatus for the extracorporeal carbamylation of sickle cells is being designed.